Paricalcitol + Chemotherapy for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Kimberly Perez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Thiazide diuretics, CYP450 3A inducers

Disqualifiers: Brain metastases, Hypercalcemia, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adding a form of vitamin D to usual cancer treatment can improve treatment for patients with advanced pancreatic cancer. Pancreatic cancer is very aggressive, and current treatments are not very effective. This form of vitamin D might help by blocking signals that make cancer cells grow and spread.

Will I have to stop taking my current medications?

The trial requires you to stop taking vitamin D and calcium supplements, as well as thiazide diuretics (a type of medication for high blood pressure) before starting the treatment. Additionally, you cannot take medications that affect the CYP450 3A enzyme, so you should check with your doctor about any other medications you are taking.

What data supports the effectiveness of the drug combination of Paricalcitol and chemotherapy for pancreatic cancer?

Research shows that the combination of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine is an effective treatment for advanced pancreatic cancer, as demonstrated in multiple studies, including a global phase III trial. This combination has become a standard treatment option for metastatic pancreatic cancer due to its positive results. ^{1 2 3 4 5}

Is the combination of Paricalcitol and chemotherapy safe for treating pancreatic cancer?

The combination of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine has been studied for safety in treating pancreatic cancer, including in elderly patients and those with specific complications. These studies suggest that the treatment is generally safe, although individual tolerance may vary. ^{1 2 3 5 6}

What makes the drug Paricalcitol + Chemotherapy unique for pancreatic cancer?

This treatment combines paricalcitol with chemotherapy drugs gemcitabine and nab-paclitaxel, which is a novel approach as nab-paclitaxel is a special formulation that improves drug delivery and reduces toxicity compared to older versions, potentially enhancing effectiveness in treating pancreatic cancer. ^{1 3 7 8 9}

Research Team

Kimberly Perez, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with previously untreated, metastatic pancreatic cancer. They should have measurable disease, be in good physical condition (ECOG ≤1), and have normal organ/marrow function. Participants must not have had chemotherapy for advanced pancreatic cancer or certain other treatments recently and agree to use contraception.

Inclusion Criteria

I am 18 years old or older.

Ability to understand and the willingness to sign a written informed consent document

Agreement to use adequate contraception for the duration of study participation

Exclusion Criteria

I have high calcium levels in my blood.

I have had painful kidney or bladder stones in the last year.

I have severe nerve pain or numbness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate the safety of adding paricalcitol to gemcitabine and nab-paclitaxel

4 weeks

3 visits per cycle (in-person)

Randomized Phase 2

Evaluate the efficacy of paricalcitol when added to gemcitabine and nab-paclitaxel

Until disease progression or adverse events

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Gemcitabine
• Nab-paclitaxel
• Paricalcitol

Trial Overview The study tests adding paricalcitol (IV or Oral) to standard chemo drugs gemcitabine and nab-paclitaxel in two stages: first checking safety (run-in phase) then assessing effectiveness (randomized phase). The goal is to see if paricalcitol improves treatment outcomes.

Participant Groups

Group I: Gemcitabine + Nab-paclitaxel + Placebo Experimental Treatment 3 Interventions

* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis

Group II: Gemcitabine + Nab-paclitaxel + Paricalcitol oral Experimental Treatment 3 Interventions

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis

Group III: Gemcitabine + Nab-paclitaxel + Paricalcitol IV Experimental Treatment 3 Interventions

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

American Association for Cancer Research

Collaborator

Trials

9

Recruited

830+

Findings from Research

In a retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[2022]

Nab-paclitaxel has recently been introduced as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing promising improvements in patient outcomes after years of stagnation in treatment options.

The review highlights the unique mechanism of action of nab-paclitaxel, particularly its interaction with albumin and SPARC, which may enhance its efficacy in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. Al-Batran, SE., Geissler, M., Seufferlein, T., et al.[2015]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]